GLOBAL MARKETS FOR GENERIC DRUGS

GLOBAL MARKETS FOR GENERIC DRUGS PHM009H February 2017 Paul Evers Project Analyst ISBN: 1-62296-437-3 BCC Research 49 Walnut Park, Building 2 Wellesley, MA 02481 USA 866-285-7215 (toll-free within the USA), or (+1) 781-489-7301 www.bccresearch.com info@bccresearch.com

TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 2 STUDY GOALS AND OBJECTIVES 2 REASONS FOR DOING THE STUDY 2 SCOPE OF REPORT 3 MARKET ANALYSES AND FORECASTS 3 METHODOLOGY 3 INTENDED AUDIENCE 3 INFORMATION SOURCES 3 ANALYST'S CREDENTIALS 4 RELATED BCC RESEARCH REPORTS 4 BCC RESEARCH WEBSITE 4 DISCLAIMER 5 CHAPTER 2 SUMMARY 7 MARKET SIZE AND EVOLUTION 8 SUMMARY TABLE GLOBAL MARKET FOR GENERIC DRUGS, BY REGION, THROUGH 2021 ($ SUMMARY FIGURE GLOBAL MARKET FOR GENERIC DRUGS, BY REGION, 2014-2021 ($ 9 9 CHAPTER 3 OVERVIEW 11 TABLE 1 GLOBAL PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ RECENT HISTORY OF THE GENERICS SECTOR 13 ROCHE-BOLAR 13 GENERICS LOBBY 14 ICH 15 12 CHAPTER 4 THE NEW GENERICS ERA 17 THE PATENT CLIFF 18 TABLE 2 MAJOR RECENT AND UPCOMING PATENT EXPIRIES, 2014-2020 18 TABLE 3 BRAND SALES BEFORE AND AFTER PATENT EXPIRY ($ MILLIONS) 19 TYPES OF GENERICS 19 SIMPLE GENERICS 20 Adequate Market Size 20 Patent-expired Therapies 20 Older Products Still Used 21 Long-term Use 21 Straightforward Production Technology 21 Drugs Used in Primary Care 22 SUPERGENERICS 22 BIOSIMILARS 23 TABLE 4 BIOTHERAPEUTICS AMONG TOP 40 PRESCRIPTION PHARMACEUTICALS, 2015 ($ TABLE 5 BIOLOGICS WITH RECENT OR UPCOMING LOSS OF PATENT PROTECTION 24 SPECIAL CHALLENGES 26 24

THE BIOSIMILARS MARKET 28 Biosimilar Developments and Introductions 28 EPO 28 G-CSF 29 Interferons 29 hgh 29 Monoclonal Antibodies 29 CHAPTER 5 MAJOR GENERIC ISSUES 32 REGULATORY ENVIRONMENT 32 UNITED STATES 32 TABLE 6 REQUIREMENTS FOR NDA AND ANDA APPLICATIONS 33 EUROPEAN UNION 34 EU Marketing Authorization Systems 35 The Centralized Procedure 35 Decentralized and Mutual Recognition Procedures 36 Mutual Recognition Procedure 37 Types of Applications 37 Applications Under Article 10 (Generic Products) 38 JAPAN 38 Approval of Pharmaceuticals 39 REGULATION OF BIOSIMILARS 39 EU Provisions 40 Evolving Situation in the U.S. 40 User Fees 42 Hatch-Waxman and Bolar 42 DEFENSIVE STRATEGIES BY "BIG PHARMA" 43 "AUTHORIZED GENERICS" 44 User Fees 45 Changing Climate for Generics 45 Situation in Europe 46 PATENTS AND IP 47 SUPPLEMENTARY PROTECTION CERTIFICATES 48 CHAPTER 6 THE GENERICS MARKET 51 GLOBAL PHARMACEUTICAL AND GENERICS MARKET 51 GLOBAL GENERICS MARKET 51 MAIN NATIONAL GENERICS MARKETS 51 TABLE 7 GLOBAL MARKET FOR PHARMA AND GENERIC DRUGS, THROUGH 2021 ($ TABLE 8 GLOBAL MARKET FOR GENERIC DRUGS, BY COUNTRY, THROUGH 2021 ($ MARKET OPPORTUNITIES BY PRODUCT CLASS 52 LEADING GENERIC MOLECULES 52 TABLE 9 TOP 20 GENERIC MOLECULES, BY PRESCRIPTION SALES, 2015 ($ 53 TABLE 10 GLOBAL TOP-SELLING PRESCRIPTION PHARMACEUTICALS 54 Anti-infectives 55 TABLE 11 LEADING ANTI-INFECTIVE PRODUCT SALES, 2015 ($ MILLIONS) 56 52 52

CNS Therapies 56 Antidepressants 57 Antipsychotics 58 TABLE 12 LEADING CNS PRODUCT SALES, 2015 ($ MILLIONS) 58 Anxiolytics 59 Sleep Disorders 59 Epilepsy 60 Parkinson's Disease 61 Migraine 61 Cardiovascular Products 61 TABLE 13 LEADING CARDIOVASCULAR PRODUCT SALES, 2015 ($ MILLIONS) 62 Anti-arthritis Products 63 Steroids 63 NSAIDs 63 COX-II Inhibitors 64 DMARDs 65 TABLE 14 LEADING ANTI-ARTHRITIS PRODUCT SALES, 2015 ($ MILLIONS) 65 Respiratory Products 66 Asthma 66 COPD 66 Allergic Rhinitis 67 Bronchodilators 67 Inhaled bronchodilators 67 Anticholinergics 68 Oral bronchodilators 68 Leukotriene antagonists 68 Steroids 69 FIGURE 1 GLOBAL MARKET SHARE OF ASTHMA PRODUCT CATEGORIES (%) 69 TABLE 15 LEADING RESPIRATORY PRODUCT SALES, 2015 ($ MILLIONS) 70 Anticancer Products 70 Cytotoxic Drugs 70 Hormonal Therapy 71 Biologic Response Modifiers 71 Anti-angiogenesis Drugs 71 Monoclonal Antibodies 71 TABLE 16 LEADING ANTICANCER PRODUCT SALES, 2015 ($ MILLIONS) 72 CHAPTER 7 GENERICS MARKETS AND FORECASTS BY COUNTRY 75 AMERICAS 75 UNITED STATES 75 Vital Statistics 75 Health and Healthcare 75 Pharmaceutical Market 76 TABLE 17 U.S. PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Generics Market 77 Biosimilars 77 Generic Prices 77 77

"Carve-outs" 78 Generics Industry 78 The Future 79 CANADA 79 Vital Statistics 79 Pharmaceutical Market 80 TABLE 18 CANADA'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Generics Market 80 Prices of Generics 81 How Generics Are Supplied 82 BRAZIL 82 Vital Statistics 82 Pharmaceutical Market 83 TABLE 19 BRAZIL'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Generics Market 84 M&A Activity 86 Future Prospects 86 ProGenericos 87 ASIA 87 JAPAN 87 Vital Statistics 87 Health and Healthcare 87 Pharmaceutical Market 88 TABLE 20 JAPAN'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 21 TOP 25 JAPANESE PHARMA COMPANIES ($ MILLIONS/%) 89 Generics Market 90 Generics Industry 92 INDIA 93 Vital Statistics 93 Health and Healthcare 93 Growing Affluence - Changing Medical Needs 93 Pharmaceutical Market 93 TABLE 22 INDIA S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Pharma Industry 95 Patent Reform 95 Generics Industry 96 TABLE 23 LEADING PHARMA COMPANIES IN INDIA, 2012 ($ MILLIONS) 96 CHINA 97 Vital Statistics 97 Health and Healthcare 97 Pharmaceutical Market 98 TABLE 24 CHINA'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Domestic Industry 99 80 83 88 94 99

Foreign Company Involvement 100 Importance of R&D 102 Challenges 102 Market Trends 102 Regulatory Changes 103 Generics Exports 103 Domestic Generics Market 104 Local Dominance 104 EUROPE 105 FRANCE 106 Vital Statistics 106 Health and Healthcare 106 Healthcare Provision 106 FIGURE 2 HEALTH EXPENDITURE IN MAJOR EUROPEAN MARKETS AND THE U.S., 2014 (PERCENTAGE OF GDP) Pharmaceutical Market 108 TABLE 25 FRANCE'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Generics Market 108 GERMANY 110 Vital Statistics 110 Health and Healthcare 110 Provision of Healthcare 110 Pharmaceutical Market 111 Price Controls 111 TABLE 26 GERMANY S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Generics Market 113 ITALY 113 Vital Statistics 113 Health and Healthcare 114 Healthcare System 114 Pharmaceutical Market 114 TABLE 27 ITALY'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Pharmaceutical Industry 116 Generics Market 117 SPAIN 118 Vital Statistics 118 Health and Healthcare 118 Healthcare Provision 118 Pharmaceutical Services 119 Pharmaceutical Market 119 TABLE 28 SPAIN'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ Generics Market 120 106 108 112 116 120 Generics Industry 121 TABLE 29 LEADING GENERICS COMPANIES IN SPAIN, 2015 ($ MILLIONS) 121

UNITED KINGDOM 121 Vital Statistics 122 Health and Healthcare 122 Healthcare Provision 122 Private Sector Involvement 122 Pharmaceuticals 123 Pharmaceutical Market 123 TABLE 30 LEADING PHARMA COMPANIES IN THE U.K., BY MARKET SHARE, 2013 (%) 124 Generics Market 124 TABLE 31 U.K.'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ RUSSIA 126 Vital Statistics 127 Health and Healthcare 127 Healthcare Delivery 127 Pharmaceutical Market 127 Pharma 2020 128 TABLE 32 RUSSIA'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 33 LEADING PHARMA COMPANIES IN RUSSIA, BY MARKET SHARE, 2012 (%) 129 Generics Market 130 125 129 CHAPTER 8 THE GLOBAL GENERICS INDUSTRY 132 TABLE 34 LEADING GENERICS COMPANIES, BY SALES, 2015 ($ 132 TRENDS 132 STRUCTURE OF THE GENERICS INDUSTRY 133 RECENT M&A ACTIVITY 134 BRAND COMPANY INVOLVEMENT 135 PROFILES OF THE LEADING GENERICS COMPANIES 136 ACTAVIS (TEVA) 136 ASPEN PHARMACARE HOLDINGS LTD. 137 CIPLA LTD. 139 FRESENIUS KABI 140 HOSPIRA INC. 141 Biogenerics 141 Financials 142 LUPIN, LTD. 142 MYLAN INC. 143 SANDOZ INTERNATIONAL GMBH 145 Products 145 SANOFI 147 SUN PHARMACEUTICAL INDUSTRIES LTD. 148 TEVA PHARMACEUTICAL INDUSTRIES LTD. 148 Financials 150 OTHER INTERNATIONAL GENERICS COMPANIES 150 AUROBINDO PHARMA LTD. 150 DR. REDDY'S LABORATORIES LTD. 152 EGIS PHARMACEUTICALS PLC 153

APIs 154 KRKA 154 Products 155 PAR PHARMACEUTICAL, INC. 156 Generics 156 STADA ARZNEIMITTEL 157 Generics 157 Biosimilars 158 STRIDES SHASUN LTD. 159 WOCKHARDT LTD. 160 ZYDUS CADILA 161

LIST OF TABLES TABLE HEADING SUMMARY TABLE GLOBAL MARKET FOR GENERIC DRUGS, BY REGION, THROUGH 2021 ($ TABLE 1 GLOBAL PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 2 MAJOR RECENT AND UPCOMING PATENT EXPIRIES, 2014-2020 18 TABLE 3 BRAND SALES BEFORE AND AFTER PATENT EXPIRY ($ MILLIONS) 19 TABLE 4 BIOTHERAPEUTICS AMONG TOP 40 PRESCRIPTION PHARMACEUTICALS, 2015 ($ TABLE 5 BIOLOGICS WITH RECENT OR UPCOMING LOSS OF PATENT PROTECTION 24 TABLE 6 REQUIREMENTS FOR NDA AND ANDA APPLICATIONS 33 TABLE 7 GLOBAL MARKET FOR PHARMA AND GENERIC DRUGS, THROUGH 2021 ($ TABLE 8 GLOBAL MARKET FOR GENERIC DRUGS, BY COUNTRY, THROUGH 2021 ($ TABLE 9 TOP 20 GENERIC MOLECULES, BY PRESCRIPTION SALES, 2015 ($ 53 TABLE 10 GLOBAL TOP-SELLING PRESCRIPTION PHARMACEUTICALS 54 TABLE 11 LEADING ANTI-INFECTIVE PRODUCT SALES, 2015 ($ MILLIONS) 56 TABLE 12 LEADING CNS PRODUCT SALES, 2015 ($ MILLIONS) 58 TABLE 13 LEADING CARDIOVASCULAR PRODUCT SALES, 2015 ($ MILLIONS) 62 TABLE 14 LEADING ANTI-ARTHRITIS PRODUCT SALES, 2015 ($ MILLIONS) 65 TABLE 15 LEADING RESPIRATORY PRODUCT SALES, 2015 ($ MILLIONS) 70 TABLE 16 LEADING ANTICANCER PRODUCT SALES, 2015 ($ MILLIONS) 72 TABLE 17 U.S. PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 18 CANADA'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 19 BRAZIL'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 20 JAPAN'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 21 TOP 25 JAPANESE PHARMA COMPANIES ($ MILLIONS/%) 89 TABLE 22 INDIA S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 23 LEADING PHARMA COMPANIES IN INDIA, 2012 ($ MILLIONS) 96 TABLE 24 CHINA'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 25 FRANCE'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 26 GERMANY S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 27 ITALY'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 28 SPAIN'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 29 LEADING GENERICS COMPANIES IN SPAIN, 2015 ($ MILLIONS) 121 TABLE 30 LEADING PHARMA COMPANIES IN THE U.K., BY MARKET SHARE, 2013 (%) 124 TABLE 31 U.K.'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ TABLE 32 RUSSIA'S PHARMACEUTICALS AND GENERICS MARKET, THROUGH 2021 ($ 9 12 24 52 52 77 80 83 88 94 99 108 112 116 120 125 129

TABLE HEADING TABLE 33 LEADING PHARMA COMPANIES IN RUSSIA, BY MARKET SHARE, 2012 (%) 129 TABLE 34 LEADING GENERICS COMPANIES, BY SALES, 2015 ($ 132

LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE GLOBAL MARKET FOR GENERIC DRUGS, BY REGION, 2014-2021 ($ FIGURE 1 GLOBAL MARKET SHARE OF ASTHMA PRODUCT CATEGORIES (%) 69 FIGURE 2 HEALTH EXPENDITURE IN MAJOR EUROPEAN MARKETS AND THE U.S., 2014 (PERCENTAGE OF GDP) 9 106